crossing96/oncoscreening huggingface dataset:
High PDL1 mRNA expression predicts better survival of stage pT1 non-muscle-invasive bladder cancer (NMIBC) patients.	INTRODUCTION AND OBJECTIVES: Checkpoint inhibition has emerged as new therapeutic option in muscle-invasive bladder cancer. The objective of the present study was to evaluate the prognostic role of PD1 and PDL1 expression in non-muscle-invasive bladder cancer (NMIBC) and establish an objective measuring method using RNA quantification. MATERIALS AND METHODS: We retrospectively analyzed clinical data and formalin-fixed paraffin-embedded tissues (FFPE) of patients with stage pT1 NMIBC who underwent transurethral resection of the bladder. mRNA expression of PD1, PDL1 and CD3 was measured by single step RT-qPCR and correlated to clinicopathological parameters, recurrence-free survival (RFS), progression-free survival (PFS) and carcinoma-specific survival (CSS). RESULTS: We have analyzed 334 patients with NMIBC at stage pT1 for mRNA analysis. Data from 296 patients (79% male, median age: 72 years) could be used. Spearman correlation revealed significant associations between mRNA expressions of PD1/PDL1 (ρ: 0.6024, p < 0.0001), CD3/PDL1 (ρ: 0.5728, p < 0.0001) and CD3/PD1 (ρ: 0.7005, p < 0.0001). Kaplan-Meier analysis revealed that high PDL1 mRNA expression (≥ 33.83) is a favorable prognostic factor with regard to better RFS (p = 0.0018), PFS (p = 0.021) and CSS (p = 0.012). Multivariate Cox-regression analysis proved PDL1 expression to be an independent prognosticator for RFS [HR 0.48 (0.31-0.72), p = 0.0005], PFS [HR 0.45 (0.24-0.80), p = 0.0059] and CSS [HR 0.31 (0.13-0.67), p = 0.0021]. CONCLUSION: High mRNA expression of PDL1 predicts improved RFS, PFS and CSS of pT1 NMIBC. Following prospective validation, this objective measurement of PD-L1 might help stratify patients with NMIBC for immunotherapy and identify patients who might benefit from early cystectomy.	bladder
Urothelial cancer proteomics provides both prognostic and functional information.	Traditionally, bladder cancer has been classified based on histology features. Recently, some works have proposed a molecular classification of invasive bladder tumors. To determine whether proteomics can define molecular subtypes of  muscle invasive urothelial cancer (MIUC) and allow evaluating the status of biological processes and its clinical value. 58 MIUC patients who underwent curative surgical resection at our institution between 2006 and 2012 were included. Proteome was evaluated by high-throughput proteomics in routinely archive FFPE tumor tissue. New molecular subgroups were defined. Functional structure and individual proteins prognostic value were evaluated and correlated with clinicopathologic parameters. 1,453 proteins were quantified, leading to two MIUC molecular subgroups. A protein-based functional structure was defined, including several nodes with specific biological activity. The functional structure showed differences between subtypes in metabolism, focal adhesion, RNA and splicing nodes. Focal adhesion node has prognostic value in the whole population. A 6-protein prognostic signature, associated with higher risk of relapse (5 year DFS 70% versus 20%) was defined. Additionally, we identified two MIUC subtypes groups. Prognostic information provided by pathologic characteristics is not enough to understand MIUC behavior. Proteomics analysis may enhance our understanding of prognostic and classification. These findings can lead to improving diagnosis and treatment selection in these patients.	bladder
Bladder Herpes Infection in a Patient With Low-grade Non-Muscle-invasive Bladder Cancer.	Bladder herpes is a very uncommon event related to herpes simplex virus infection. We report a 69-year-old man with 4-year history of bladder cancer who presented with dysuria and urinary frequency. Cystoscopy showed erythematous lesion of the bladder mucosa that was biopsied and revealed multilobed nuclei with eosinophilic intranuclear inclusions, and presence of intracytoplasmic vacuoles that were suggestive of bladder involvement by herpes simplex virus. Different bladder disorders have been associated with herpes virus, but spontaneous resolution generally occurs in 1-2 months.	bladder
Florence robotic intracorporeal neobladder (FloRIN): a new reconfiguration strategy developed following the IDEAL guidelines.	OBJECTIVE: To describe our step-by-step technique for robotic intracorporeal neobladder configuration, including the stages of conception, development and exploration of this surgical innovation, according to the Idea, Development, Exploration, Assessment, Long-term follow-up (IDEAL) Collaboration guidelines. PATIENTS AND METHODS: The Florence robotic intracorporeal neobladder (FloRIN) was performed employing the following main surgical steps: isolation of 50 cm of ileum; bowel anastomosis; urethro-ileal anastomosis creating an asymmetrical 'U'-shape (30 cm distally and 20 cm proximally to anastomosis), ileum detubularisation; posterior wall reconfiguration as an 'L'; bladder neck reconstruction; anterior folding of the posterior plate to reach the 12 o'clock position; uretero-enteral 'orthotopic' bilateral anastomosis. The conception and development of the FloRIN followed the IDEAL guidelines recommended stages: Phase 1 (simulation) involved the neobladder robotic configuration using silicone models. Phase 2a (development) aimed to reproduce the configuration in an open fashion in one patient, and then in the first three robotic procedures. Phase 2b (exploration) consisted of the technique standardisation in 15 consecutive robotic approaches. Phase 2a and 2b included urodynamics and imaging assessment of the patients treated. RESULTS: From February 2016 to September 2017 FloRIN was performed in 18 patients. Comparing the first three (Phase 2a) with the subsequent 15 patients (Phase 2b), the median (interquartile range [IQR]) reconstruction operating time was 260 (220-340) vs 160 (150-210) min, respectively. Postoperative surgical complications occurred in four of the 18 patients (22.1%), including one surgical Clavien-Dindo Grade III and three Grade I, postoperative medical Clavien-Dindo Grade II complications occurred in three (16.7%) patients. On urodynamic examination (available in nine [50%] patients) the median (IQR) reservoir cystometric capacity, compliance, and post-void residual were 240 (220-267) mL, 18 (12.5-19.8) mL/cmH(2) O, and 0 (0-50) mL, respectively. Ultrasonography showed no Grade ≥2 vesico-ureteric reflux. CONCLUSION: We describe the FloRIN configuration, showing its technical feasibility with acceptable time efficiency. The first cases studied had good reservoir capacity, low pressure with no reflux, and complete voiding.	bladder
Primary Malignant Melanoma of the Bladder.	A 81-year-old man was admitted to our university for a second opinion after diagnosis of bladder melanoma in December 2014. His medical history included arterial hypertension, hypothyroidism, peripheral arterial disease treated with a bypass, and corneal transplantation. His medical history was negative for malignant melanoma. He experienced gross hematuria in the absence of any other clinical manifestations, and urine cytology identified atypical cells. The patient underwent transurethral resection of the bladder with diagnosis of melanoma.	bladder
Biodistribution of gold nanoparticles in BBN-induced muscle-invasive bladder cancer in mice.	Bladder-sparing options are being developed for muscle-invasive bladder cancer in place of radical cystectomy, including the combination of chemotherapy and radiation therapy. We reasoned that improving the radiotherapy component of chemoradiation could improve the control of locally advanced disease. Previously, we showed that gold nanoparticles (AuNPs) are potent enhancers of radiation therapy. We hypothesized that if AuNPs were to preferentially localize to bladder tumors, they may be used to enhance the radiation component of muscle-invasive bladder tumor therapy. Mice were treated with the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 17, 20, and 22 weeks - long enough to induce muscle-invasive tumors. Mice were then anesthetized and injected intravenously with 1.9 nm AuNPs of which most were rapidly cleared from the blood and excreted after a 30-50 minute residence time in the bladder. We found AuNPs distributed throughout the bladder wall, but most of the AuNPs were associated with the stroma surrounding the tumor cells or extracellular keratin produced by the tumor cells. There were relatively few AuNPs in the tumor cells themselves. The AuNPs therefore localized to tumor-associated stroma and this tumor specificity might be useful for specific X-ray dose enhancement therapy of muscle-invasive bladder carcinomas.	bladder
The Rho GTPase signalling pathway in urothelial carcinoma.	Urothelial carcinoma remains a clinical challenge: non-muscle-invasive disease has a high rate of recurrence and risk of progression, and outcomes for patients with advanced disease are poor, owing to a lack of effective systemic therapies. The Rho GTPase family of enzymes was first identified >30 years ago and contains >20 members, which are divided into eight subfamilies: Cdc42, Rac, Rho, RhoUV, RhoBTB, RhoDF, RhoH, and Rnd. Rho GTPases are molecular on-off switches, which are increasingly being understood to have a critical role in a number of cellular processes, including cell migration, cell polarity, cell adhesion, cell cycle progression, and regulation of the cytoskeleton. This switch is an evolutionarily conserved system in which GTPases alternate between GDP-bound (inactive) and GTP-bound (active) forms. The activities of these Rho GTPases are many, context-dependent, and regulated by a number of proteins that are being progressively elucidated. Aberrations of the Rho GTPase signalling pathways have been implicated in various malignancies, including urothelial carcinoma, and understanding of the role of Rho GTPases in these diseases is increasing. This signalling pathway has the potential for therapeutic targeting in urothelial carcinoma. Research in this area is nascent, and much work is necessary before current laboratory-based research can be translated into the clinic.	bladder
High-Grade Urothelial Carcinoma on Urine Cytology Resembling Umbrella Cells.	CONTEXT: High-grade urothelial carcinoma (UC) cells have many appearances on urine cytology, but according to The Paris System, they can be easily distinguished from umbrella cells. OBJECTIVE: We aimed to define the incidence and appearance of high-grade UC cells that resemble umbrella cells in Cytospin preparations on urine cytology. RESULTS: Cytospin preparations from 331 cases with biopsy follow-up (230 benign/low-grade and 101 malignant [22 carcinoma in situ, 52 papillary, 19 invasive UC, 8 other] cases) were reviewed. A total of 18 cases with malignant cells resembling umbrella cells were identified (17.8% of the malignant cases) and were the only type of malignant cell in 3% of the cases. Two patterns were identified. Tumor cells were either identifiable by at least 20 abnormal cells which were large, had abundant cytoplasm but an elevated nuclear-to-cytoplasmic ratio, and markedly enlarged, round-to-elongated nucleoli, or else rare cells with abundant cytoplasm but obviously malignant nuclei. Cells without nucleoli or obviously malignant nuclei were not specific. CONCLUSIONS: Malignant cells resembling umbrella cells can be seen in up to 17% of urine cytology specimens.	bladder
Recent Developments in the Search for Urinary Biomarkers in Bladder Cancer.	PURPOSE OF REVIEW: This review aims to evaluate research surrounding the utility of urinary biomarkers to detect bladder cancer and predict recurrence. RECENT FINDINGS: Recent research has focussed on the evaluation of genetic markers found in urine to provide diagnostic and prognostic information. Furthermore, the isolation and characterisation of extracellular vesicles (EVs) from the urine patients with bladder cancer provide an exciting new development in biomarker research that is set to expand in the coming years. Current urinary biomarker research is a broad field that encompasses the evaluation of urinary proteins, DNA, RNA and EVs to detect signatures that can be used to predict the presence of bladder cancer and provide prognostic information. EVs in particular offer an exciting and novel perspective in the search for accurate bladder cancer biomarkers.	bladder
Contrast-enhanced ultrasound of small cell carcinoma in urinary bladder: a case report and review of literature.	BACKGROUND: Small cell carcinoma of the urinary bladder (SCCB) is a relatively rare malignant bladder tumor, and few reports have investigated the microvasculature of SCCB imaged using contrast-enhanced ultrasound (CEUS). CASE PRESENTATION: A 63-year-old female was admitted to our hospital after experiencing painless gross hematuria for one week. The gray-scale ultrasound (US) demonstrated a 4.8 × 3.4 × 3.6-cm(3) hypoechoic mass in the apex of the urinary bladder with a wide base and an irregular surface; the mass did not move with changes in body position. Color Doppler flow imaging (CDFI) showed rich blood flow in the mass. CEUS with low mechanical index (MI) of 0.06 confirmed a highly enhanced 5.0 × 3.3 × 3.8 cm(3) mass within the bladder at the apex wall. The time-intensity curves (TICs) showed a wash-in time of 10 s, a time to peak (TTP) of 33 s, a signal intensity (SI) of 62.7% and a wash-out time > 60 s. Finally, the transurethral resection of the bladder tumor (TURBT) was performed, and the pathological examination proved the diagnosis of SCCB. CONCLUSION: CEUS can provide valuable information related to the rich microvasculature of SCCB, which may be helpful in its diagnosis.	bladder
YRNA expression predicts survival in bladder cancer patients.	BACKGROUND: Non-coding RNAs play an important role in human carcinogenesis. YRNAs (Ro-associated Y), a novel class of non-coding RNAs, have been identified as biomarker in various malignancies, but remain to be studied in urinary bladder cancer (BCA) patients. METHODS: The expression of all four YRNAs (RNY1, RNY3, RNY4, RNY5) was determined in archival BCA (urothelial carcinoma, n = 88) and normal urothelial bladder (n = 30) tissues using quantitative real-time PCR. Associations with clinicopathological parameters and prognostic role for overall and cancer-specific survival were analysed. RESULTS: All YRNAs were significantly downregulated in BCA tissue. A low expression of RNY1, RNY3 and RNY4 was associated with muscle-invasive BCA, lymph node metastases and advanced grade. Furthermore, expression of RNY1 and RNY3 was predictive for BCA patients' overall (also RNY4) and cancer-specific survival as estimated using Kaplan-Meier and univariate (but not multivariate) Cox regression analyses. RNY1, RNY3 and RNY4 show good discriminative ability between tumor and normal tissue, as well as between muscle-invasive and non-muscle-invasive urothelial carcinoma. CONCLUSIONS: The expression of YRNAs is altered in BCA and associated with poor prognosis. Possible diagnostic role of YRNAs should be investigated in further studies.	bladder
Circular RNA hsa_circ_0003221 (circPTK2) promotes the proliferation and migration of bladder cancer cells.	Emerging studies have shown that circular RNAs could be ideal biomarkers and even potential therapeutic targets for some tumors, including bladder cancer. However, only a few studies have investigated the circular RNAs in human bladder cancer. The key circular RNA molecules are closely related to bladder cancer and their roles remain largely unknown. Here, we investigated a novel circular RNA molecule, hsa-circ-0003221(circPTK2), which is differentially expressed in bladder carcinoma. Significant differential expression levels of circPTK2 were confirmed with quantitative PCR in 40 pairs of tissue and blood samples from patients with bladder carcinoma. Moreover, circPTK2 levels both in tissue and blood were significantly correlated with several clinicopathologic characteristics, including poor differentiation (P = 0.0103 in tissue, P = 0.024 in blood), N2-N3 lymph node metastasis (P = 0.0065 in tissue, P = 0.016 in blood), and T(II-III-IV) stage (P = 0.008 in tissue, P = 0.0003 in blood). Quantitative PCR results confirmed that circPTK2 is highly expressed in migrated cells separated by Transwell assay and in metastatic lymph nodes of tumors transplanted in nude mice. In vitro silence of circPTK2 by small interfering RNA inhibited the proliferation and migration of bladder cancer cells. On the contrary, circPTK2 overexpression promoted proliferation and migration. This study showed that circPTK2 promotes proliferation and migration of cells and may be a novel potential biomarker and therapeutic target for bladder cancer diagnosis and therapy.	bladder
Prostaglandin receptors induce urothelial tumourigenesis as well as bladder cancer progression and cisplatin resistance presumably via modulating PTEN expression.	BACKGROUND: We investigated the role of prostaglandin receptors (e.g. prostaglandin E2 receptor 2 (EP2), EP4) and the efficacy of celecoxib in urothelial tumourigenesis and cancer progression. METHODS: We performed immunohistochemistry in bladder cancer (BC) tissue microarrays, in vitro transformation assay in a normal urothelial SVHUC line, and western blot/reverse transcription-polymerase chain reaction/cell growth assays in BC lines. RESULTS: EP2/EP4 expression was elevated in BCs compared with non-neoplastic urothelial tissues and in BCs from those who were resistant to cisplatin-based neoadjuvant chemotherapy. Strong positivity of EP2/EP4 in non-muscle-invasive tumours or positivity of EP2/EP4 in muscle-invasive tumours strongly correlated with disease progression or disease-specific mortality, respectively. In SVHUC cells, exposure to a chemical carcinogen 3-methylcholanthrene considerably increased and decreased the expression of EP2/EP4 and phosphatase and tensin homologue (PTEN), respectively. Treatment with selective EP2/EP4 antagonist or celecoxib also resulted in prevention in 3-methylcholanthrene-induced neoplastic transformation of SVHUC cells. In BC lines, EP2/EP4 antagonists and celecoxib effectively inhibited cell viability and migration, as well as augmented PTEN expression. Furthermore, these drugs enhanced the cytotoxic activity of cisplatin in BC cells. EP2/EP4 and PTEN were also elevated and reduced, respectively, in cisplatin-resistant BC sublines. CONCLUSIONS: EP2/EP4 activation correlates with induction of urothelial cancer initiation and outgrowth, as well as chemoresistance, presumably via downregulating PTEN expression.	bladder
A Method for Cross-Species Visualization and Analysis of RNA-Sequence Data.	In this methods article, I describe a computational workflow for cross-species visualization and comparison of mRNA-seq transcriptome profiling data. The workflow is based on gene set variation analysis (GSVA) and is illustrated using commands in the R programming language. I provide a complete step-by-step procedure for the workflow using mRNA-seq data sets from dog and human bladder cancer as an example.	bladder
Potentialities of MicroRNA Diagnosis in Patients with Bladder Cancer.	Despite promising vista of the use of microRNA in molecular diagnosis of bladder cancer, there are few data on their expression profiles, which impedes assessment of diagnostic value of these marker molecules. In this study, suppression subtractive hybridization, on-chip hybridization, and high-throughput deep sequencing focused on profiling microRNA and assessing the diagnostic value of revealed marker molecules.	bladder
Astrocyte elevated gene-1 promotes invasion and epithelial-mesenchymal transition in bladder cancer cells through activation of signal transducer and activator of transcription 3.	OBJECTIVES: To determine the impact of astrocyte elevated gene-1 on the invasion and epithelial-mesenchymal transition of bladder cancer cells in vitro and metastasis in vivo. METHODS: Gain- and loss-of-function studies were carried out to investigate the biological roles of astrocyte elevated gene-1 in bladder cancer cell invasion, epithelial-mesenchymal transition and lung metastasis. The mechanism underlying the activity of astrocyte elevated gene-1 was examined. RESULTS: Overexpression of astrocyte elevated gene-1 led to a significant increase in the invasive ability of UMUC3 and T24 bladder cancer cells in Matrigel invasion assays. In contrast, silencing of astrocyte elevated gene-1 restrained bladder cancer cell invasion. Overexpression of astrocyte elevated gene-1 downregulated E-cadherin and upregulated vimentin and Twist1, while silencing of astrocyte elevated gene-1 exerted an opposite effect. Mechanistically, astrocyte elevated gene-1 overexpression promoted the phosphorylation of signal transducer and activator of transcription 3 in bladder cancer cells. Treatment with WP1066, a specific signal transducer and activator of transcription 3 inhibitor, significantly abolished astrocyte elevated gene-1-induced invasion and epithelial-mesenchymal transition in UMUC3 cells. In vivo studies showed that astrocyte elevated gene-1 overexpression stimulated the growth of UMUC3 xenograft tumors and lung metastasis. CONCLUSIONS: Astrocyte elevated gene-1 shows the ability to promote bladder cancer metastasis, which is causally linked to induction of signal transducer and activator of transcription 3 activation and epithelial-mesenchymal transition. Therefore, targeting astrocyte elevated gene-1 might offer therapeutic benefits in treating metastatic bladder cancer.	bladder
Prognostic and Predictive Value of O(6)-methylguanine Methyltransferase for Chemotherapy in Patients with Muscle-Invasive Bladder Cancer.	PURPOSE: DNA repair genes are potential biomarkers for chemotherapy in muscle-invasive bladder cancer (MIBC). O(6)-methylguanine methyltransferase (MGMT) is involved in DNA repair and is found to affect the efficacy of platinum-based chemotherapy. However, the prognostic or predictive value of MGMT expression in chemotherapy for MIBC is unknown. MATERIALS AND METHODS: Immunohistochemical staining for MGMT was performed in paraffin-embedded tumor tissue of high-grade MIBC patients who underwent cystectomy in two independent cohorts [n = 74 for Fudan University Shanghai Cancer Center (FUSCC) cohort and n = 115 for Zhongshan Hospital (ZS) cohort]. MGMT messenger RNA (mRNA) analysis was conducted using patients' clinical and fragments per kilobase of exon model per million mapped fragments mRNA data from The Cancer Genome Atlas (TCGA) database (n = 245). RESULTS: In our cohorts, high MGMT expression was significantly correlated with shorter overall survival (OS) in patients with platinum-based adjuvant chemotherapy [hazard ratio (HR) 2.386, p = 0.048; HR 2.920, p = 0.007; HR 2.324, p = 0.004, respectively, in FUSCC, ZS, and combination sets], but not in patients without chemotherapy. These findings were corroborated by the TCGA set (HR 1.952 and 0.697 for patients with and without chemotherapy, respectively). The chemotherapy-MGMT interaction for OS was significant in both the surgery set (p = 0.045) and TCGA set (p = 0.034). CONCLUSIONS: We demonstrated that high MGMT expression is an independent poor prognostic factor in MIBC patients with platinum-based adjuvant chemotherapy, but not in patients without chemotherapy. MGMT expression may be a potential predictor for administration of adjuvant chemotherapy.	bladder